Acute haemodynamic effects and pharmacokinetics of ramipril in patients with heart failure : a placebo controlled three-dose study

• Published in: European journal of clinical pharmacology 1993-10, Vol.45 (3), p.241-246
• Main Authors: BEERMANN, B, NYQUIST, O, HÖGLUND, C, JACOBSSON, K.-A, NÄSLUND, U, JENSEN-URSTAD, M
• Format: Article
• Language: English
• Subjects: Administration, Oral; Adult; Aged; Angiotensin-Converting Enzyme Inhibitors - pharmacokinetics; Angiotensin-Converting Enzyme Inhibitors - pharmacology; Biological and medical sciences; Blood Pressure - drug effects; Cardiovascular system; Double-Blind Method; Heart Failure - metabolism; Heart Failure - physiopathology; Hemodynamics - drug effects; Humans; Male; Medical sciences; Metabolic Clearance Rate; Pharmacology. Drug treatments; Pulmonary Wedge Pressure - drug effects; Ramipril - administration & dosage; Ramipril - analogs & derivatives; Ramipril - pharmacokinetics; Ramipril - pharmacology; Vascular Resistance - drug effects; Vasodilator agents. Cerebral vasodilators
• ISSN: 0031-6970; 1432-1041
• DOI: 10.1007/BF00315390

The aim of the present study was primarily to evaluate the haemodynamic effects of the ACE-inhibitor ramipril which is active via its metabolite ramiprilat. Ramipril 1.25, 2.5 and 5 mg and placebo was administered orally to 4 groups of 12 patients with heart failure (NYHA III) in a double-blind randomised, parallel study. Haemodynamics were monitored for 24 h and blood was sampled and urine collected for up to 96 h. In the placebo-treated group the cardiac index (CI) was significantly increased (15.8%) and right atrial pressure decreased (26.6%). Ramipril 1.25 mg had insignificant haemodynamic effects compared to placebo and the 2.5 mg dose had significant effects on some haemodynamic variables. Ramipril 5 mg had pronounced and sustained effects on pulmonary artery pressure, which fell by 43.7%, and pulmonary capillary wedge pressure (PCWP; -59.1%); systemic vascular resistance was also decreased 21%. A significant effect on CI was only seen after 2.5 mg ramipril (+7.4%). The mean maximal degree of ACE inhibition was 73.2, 90.4 and 98.5%, respectively, after the three doses of ramipril. Complete inhibition of ACE-activity was seen at a mean plasma concentration of ramiprilat of 4.7 ng.ml-1. The degree of inhibition declined with a half life of about 75 h. There was a significant relation between the degree of ACE-inhibition and change in PCWP but not with the change in SVR. Ramipril was mainly eliminated in the form of ramiprilat and inactive metabolites.